ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.560C>T (p.Thr187Ile) (rs371583734)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181069 SCV000233345 uncertain significance not specified 2017-02-01 criteria provided, single submitter clinical testing p.Thr187Ile (ACA>ATA): c.560 C>T in exon 6 of the COL3A1 gene (NM_000090.3) The T187I variant in the COL3A1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although the T187I variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure, the T187 residue is not well conserved across species. In silico analysis predicts T187I is not damaging to the protein structure/function. Nevertheless, mutations in nearby residues (G183S, G183C, G183D, G192V) have been reported in association with EDS type IV, supporting the functional importance of this region of the protein. The T187I variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in TAAD panel(s).
Integrated Genetics/Laboratory Corporation of America RCV000586266 SCV000695377 benign not provided 2017-07-10 criteria provided, single submitter clinical testing
Invitae RCV000698663 SCV000827343 uncertain significance Ehlers-Danlos syndrome, type 4 2018-10-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 187 of the COL3A1 protein (p.Thr187Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs371583734, ExAC 0.07%). This variant has been observed in an individual affected with Marfan syndrome (PMID: 25944730). ClinVar contains an entry for this variant (Variation ID: 199711). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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